Fig. 1: dACE2 is a novel truncated virally induced isoform of ACE2.
a, A UCSC Genome Browser view of the human ACE2 region (chrX: 15,560,521–15,602,580, GRCh38/hg38) showing alternative first exons ACE2-Ex1a, ACE2-Ex1b and Ex1c, a novel first exon that creates a truncated ACE2 isoform designated as dACE2. The combination of various ENCODE epigenetic marks for human cells, with H3K4me1, H3K4me3 and H3K27ac shown as peaks, and a cluster of DNase I hypersensitivity sites shown as bars indicates that dACE2-Ex1c is located within a putative regulatory region that can affect gene expression. The DNase I hypersensitivity site overlying Ex1c is detected in 38 of 95 cell lines tested. b, RNA-seq Sashimi plots depicting splicing patterns defining ACE2 and dACE2 isoforms in SeV/mock-infected T47D cells and uninfected RT-4 cells. The numbers on the Sashimi plots indicate the counts of exon–exon splicing reads. c, ACE2 is a single-span transmembrane protein with a signal peptide (SigP) of 17 aa and four functional domains—peptidase ___domain (PD, aa 18–615), collectrin-like ___domain (CLD, aa 616–740), transmembrane ___domain (TM, aa 741–761) and intracellular ___domain (ICD, aa 762–805). In dACE2, the signal peptide is not predicted; the peptidase ___domain starts from aa R357; the first 356 aa are replaced by 10 aa of a unique protein sequence; * and ** mark cleavage sites of the membrane-bound proteases ADAM17 and TMPRSS2, respectively. d,e, Sequence alignments of the 5' UTR (d) and protein sequences encoded by dACE2-Ex1c and part of the downstream exon (e) in select primates. TSS, transcription start site. dACE2 is not predicted to be encoded in any non-primate species. Additional alignment analyses are shown in Supplementary Fig. 1a,b.
